Chilton F.H.,The Center for Botanical Lipids and Inflammatory Disease Prevention |
Murphy R.C.,University of Colorado at Denver |
Wilson B.A.,Molecular Medicine and Translational science |
Sergeant S.,The Center for Botanical Lipids and Inflammatory Disease Prevention |
And 3 more authors.
Nutrients | Year: 2014
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations. © 2014 by the authors; licensee MDPI, Basel, Switzerland.
PubMed | The Center for Botanical Lipids and Inflammatory Disease Prevention and Section on Comparative Medicine
Type: | Journal: Physiology & behavior | Year: 2016
Deficiencies in omega-3 (n-3) long chain polyunsaturated fatty acids (LC-PUFAs) and increases in the ratio of omega-6 (n-6) to n-3 LC-PUFAs in brain tissues and blood components have been associated with psychiatric and developmental disorders. Most studies have focused on n-3 LC-PUFA accumulation in the brain from birth until 2years of age, well before the symptomatic onset of such disorders. The current study addresses changes that occur in childhood and adolescence. Postmortem brain (cortical gray matter, inferior temporal lobe; n=50) and liver (n=60) from vervet monkeys fed a uniform diet from birth through young adulthood were collected from archived tissues. Lipids were extracted and fatty acid levels determined. There was a marked reduction in the ratio of n-6 LC-PUFAs, arachidonic acid (ARA) and adrenic acid (ADR), relative to the n-3 LC-PUFA, docosahexaenoic acid (DHA), in temporal cortex lipids from birth to puberty and then a more gradual decrease though adulthood. This decrease in ratio resulted from a 3-fold accumulation of DHA levels while concentrations of ARA remained constant. Early childhood through adolescence appears to be a critical period for DHA accretion in the cortex of vervet monkeys and may represent a vulnerable stage where lack of dietary n-3 LC-PUFAs impacts development in humans.
PubMed | The Center for Botanical Lipids and Inflammatory Disease Prevention and Johns Hopkins University
Type: Journal Article | Journal: Current nutrition reports | Year: 2014
PubMed | The Center for Botanical Lipids and Inflammatory Disease Prevention
Type: Journal Article | Journal: The British journal of nutrition | Year: 2012
Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individuals innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 79 (sd 21), AfAm 98 (sd 19) % of total fatty acids; P < 229 10) and the AA:n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 54 (sd 22), AfAm 69 (sd 22); P = 144 10). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo--linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 63 (sd 10); GG 85 (sd 21); P = 30 10) and AA:DGLA ratios (TT 34 (sd 08), GG 65 (sd 23); P = 22 10) but higher DGLA levels (TT 19 (sd 04), GG 14 (sd 04); P = 33 10) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (081) compared with EAm (046). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.